Epigenetic regulation and cell fate determination of hematopoietic stem cell in stress conditions

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02952
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kumamoto University
• Principal Investigator: Sashida Goro 熊本大学, 国際先端医学研究機構, 特別招聘教授 (70349447)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: HMGA2 / クロマチン / TNFa / 5-FU / RFX5 / CK2

Outline of Final Research Achievements

Tissue stem cells are self-renewing and multipotent cells that maintain developmental and adult tissue homeostasis and are essential cells that repair stress-induced organ damage. To understand the molecular basis of stem cell self-renewal and differentiation, symmetric and asymmetric division of stem cells, and maintenance and regeneration of hematopoietic tissues under steady-state and stress conditions, we analyzed the stem cell regulatory mechanisms in stress hematopoiesis by HMGA2 chromatin modifier. We found the molecular basis of hematopoietic regulation by the TNFa-CK2-HMGA2 pathway, which specifically acts in hematopoietic stem cell under stress conditions.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

造血は、造血幹細胞と骨髄ニッチや骨髄細胞が、老化を含めた様々な状況に応じて相互に関連することで精密に維持されている。ただし、定常状態とストレス状態に応じて、造血幹細胞が自己複製と分化を使い分ける制御機構は、骨髄・組織レベルはもとより、幹細胞レベルですら明白ではない。本研究によって、幹細胞研究の積年の課題である「幹細胞の運命制御」の解明に貢献できた。また、将来、ストレス暴露後の造血障害を速やかに再生するための標的因子や新規治療開発への貢献も期待できる。